Study of Revlimid With Doxil and Avastin for Patients With Platinum Resistant Ovarian Cancer

Phase 1

Terminated

• Conditions: Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma
• Interventions: Drug: Lenalidomide, Liposomal Doxorubicin, Bevacizumab; Drug: Revlimid, Doxil, Avastin

• Registration Number: NCT01202890
• Lead Sponsor: New Mexico Cancer Care Alliance

Brief Summary

This study will test the feasibility of combining 3 drugs, Revlimid with Doxil and Bevacizumab,and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.

Detailed Description

The combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible tumoral interstitial pressure via increased half-life (if liposomal egress is diminished) and decreased \[42\], 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Lenalidomide has also antiangiogenic properties, with a different mechanism of action than Avastin. Given the preliminary results of the effect of the combination of Doxil with Avastin, showing an increase in progression-free survival, we are interested in using a new thalidomide analog to maximize the angiogenic inhibition. This study will test the feasibility of combining all 3 drugs, and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-14
• Study First Submitted QC: 2010-09-15
• Study First Posted: 2010-09-16
• Primary Completion: 2011-05
• Study Completion: 2012-05
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-07
• Last Update Posted: 2014-01-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 1

Inclusion Criteria

• EOC patients must be platinum resistant/refractory (see 1.1 for definition) and be considered by the attending physician capable of being treated in this study according to GCP.
• Measurable disease by RECIST criteria or evaluable disease by GCIC criteria
• No prior anthracycline or lenalidomide use, unless the dose received was equal or less than one cycle and the patient did not progress on treatment.
• Subjects must have calculated creatinine clearance > 60ml/min by Cockcroft-Gault formula during the escalation phase.
• Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula during the expansion phase. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance > 30ml/min and < 60ml/min.
• Understand and voluntarily sign an informed consent form.
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
• No contraindication to anticoagulation

Exclusion Criteria

• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
• Concurrent use of other anti-cancer agents or treatments.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• History of thromboembolic event within the last 3 months
• Known hypersensitivity to any component of Avastin

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	Revlimid, Doxil, Avastin	At the expansion phase: Revlimid 20 mg (days 1-21), Doxil 30 mg/m2 on Day 1 and Avastin 15 mg/kg on Day 1, every 3 weeks. If this regimen is not cumulatively tolerable, Avastin will be administered every other course. Patients will be received up to 6 cycles or disease progression, followed by Revlimid maintenance at 25 mg PO q Day for 3 weeks every 4 weeks in patients with stable disease.
Arm 1	Lenalidomide, Liposomal Doxorubicin, Bevacizumab	At the expansion phase: Revlimid 20 mg (days 1-21), Doxil 30 mg/m2 on Day 1 and Avastin 15 mg/kg on Day 1, every 3 weeks. If this regimen is not cumulatively tolerable, Avastin will be administered every other course. Patients will be received up to 6 cycles or disease progression, followed by Revlimid maintenance at 25 mg PO q Day for 3 weeks every 4 weeks in patients with stable disease.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of the 3 drug combination and recommend a dose for phase II studies.	6-8 months

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) after treatment with Revlimid plus Avastin and Doxil.	6-8 Months
Acute and subacute toxicities of Lenalidomide plus Doxil and Avastin for the treatment of ovarian cancer.	6-8 Months

Trial Locations

Locations (1)

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States